Search Results (11,569)

Influenza A viruses that cause pandemics, as well as other harmful pathogens (e.g., SARS-CoV-2 variants), are known as the ‘silent bioterrorists’ of the 21st century. Due to high mutability, anti-influenza chemotherapeutic treatment is a vital defense strategy to combat both seasonal and pandemic influenza strains, especially when vaccines fail. Consequently, the development of novel therapies to combat this serious threat is of great concern. Hence, in this study, 3-(2-thienyl) acrylic acid (TA) was converted into amides of anti-influenza drugs (aminoadamantanes and oseltamivir) through TBTU-mediated coupling. The crystal structures of the thienyl-based amide hybrids (TA-Am (1), TA-Rim (2), TA-Os-OEt (3), and TA-OsC (4)) were also investigated using single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Moreover, the antiviral activities of the hybrids against influenza virus A/Fort Monmouth/1/1947 (H1N1), clinically isolated influenza strain A/Wuhan/359/1995 (H3N2), and oseltamivir-resistant A/Jinnan/15/2009 (H1N1) were evaluated in vitro. Amongst the tested thienyl-based amides, bisamide 8 (Boc-Os-Hda-TA) exhibited the most potent activity against influenza virus A (A/Wuhan/359/1995) with an IC₅₀ value of 18.52 μg/mL and a selectivity index (SI) = 13.0. Full article

The construction industry faces persistent challenges, including low productivity, high waste generation, and resistance to technological innovation. Off-site modular construction, supported by Building Information Modeling (BIM), emerges as a promising strategy to address these issues and advance sustainability goals. This study aims to evaluate the practical impacts of industrialized off-site construction in the Brazilian context, focusing on cost, execution time, structural weight, and architectural–logistical constraints. The novelty lies in applying the methodology to a high standard, mixed-use multifamily building, an atypical scenario for modular construction in Brazil, and employing a MultiCriteria Decision Analysis (MCDA) to integrate results. A detailed case study is developed comparing conventional and off-site construction approaches using BIM-assisted analyses for weight reduction, cost estimates, and schedule optimization. The results show an 89% reduction in structural weight, a 6% decrease in overall costs, and a 40% reduction in project duration when adopting fully off-site solutions. The integration of results was performed through the Weighted Scoring Method (WSM), a form of MCDA chosen for its transparency and adaptability to case studies. While this study defined weights and scores, the framework allows the future incorporation of stakeholder input. Challenges identified include the need for early design integration, transport limitations, and site-specific constraints. By quantifying benefits and limitations, this study contributes to expanding the understanding of off-site modular adaptability of construction projects beyond low-cost housing, demonstrating its potential for diverse projects and advancing its implementation in emerging markets. Beyond technical and economic outcomes, the study also frames off-site modular construction within the three pillars of sustainability. Environmentally, it reduces structural weight, resource consumption, and on-site waste; economically, it improves cost efficiency and project delivery times; and socially, it offers potential benefits such as safer working conditions, reduced urban disruption, and faster provision of community-oriented buildings. These dimensions highlight its broader contribution to sustainable development in Brazil. Full article

Objectives: Overall survival (OS) of patients with stage 0 adenocarcinoma in situ (AIS) of the lung is not well characterized in the U.S. Specifically, there are a lack of data regarding the OS of patients with stage 0 AIS who do not receive treatment. We compared OS among stage 0 AIS patients who received surgery and those who received no treatment. Methods: OS of patients with stage 0 (TIS, N0, M0) AIS of the lung who received surgery versus no treatment from 2010 to 2018 in the National Cancer Data Base was evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Predictors of surgery were evaluated using multivariable logistic regression. Survival outcomes based on surgical approach were evaluated in a propensity score-matched subgroup analysis. Results: Of the 897 patients who were diagnosed with stage 0 AIS, 716 (79.8%) underwent surgical resection. A propensity score-matched analysis of 134 patients who received no treatment and 134 patients who underwent surgery showed that the surgical group had a significantly improved OS at five-years 85.8% (95% CI: 74.2–92.4%) compared to the group who received no treatment 62.8% (95% CI: 50.1–72.7%) (log-rank, p < 0.0001). Subgroup propensity score-matched analysis showed no significant differences in OS at five-years in the surgical group consisting of 201 patients who underwent a wedge resection 90.8% (95% CI: 83.8–94.8) compared to 201 patients who underwent a lobectomy 94.9% (95% CI: 89.9–97.4%) (log-rank, p = 0.19). Conclusions: In this national analysis, stage 0 AIS patients who underwent surgery had significantly better OS when compared to patients who did not receive treatment. Full article

Background/Objectives: Neuroendocrine neoplasms (NENs) of the rectum (rNEN) are a rare and heterogeneous group of tumors that can vary greatly in their biological behavior, from benign to highly aggressive. While small and well-differentiated tumors can often be handled endoscopically and still face a very good prognosis, tumor size, and grade, as well as lymph node and distant metastasis, are known risk factors for impaired prognosis. This study aimed at the identification of further prognostic factors in rNEN. Methods: A retrospective analysis of patients treated for rNEN at the ENTES Center of Excellence at Charité—Universitätsmedizin, including n = 121 patients, was performed to identify risk factors for recurrence, progression, and impaired outcome. Results: Progression-free survival (PFS) and overall survival (OS) differed significantly according to tumor grade (p < 0.001). In rNET patients undergoing surgery, the Ki-67 index and distant metastases were independent risk factors for shorter PFS. Among stage I rNETs, 10 patients developed disease recurrence, associated with lymphatic invasion (1.9% vs. 30.0%, p = 0.008) and higher Ki-67 values (2 (1–6) vs. 2 (1–16), p = 0.054). Conclusions: Tumor grade and presence of metastases represent important predictive factors in rNEN. Notably, even small, early-stage rNETs can harbor a risk of recurrence when unfavorable pathological features are present, highlighting the importance of tailored, risk-adapted surveillance strategies to optimize patient outcomes. Full article

Background: Lung cancer has the highest lethality rate among malignancies worldwide. Immunotherapy is one of the common treatments for lung cancer patients. There are two main types of immunotherapies: one targets programmed cell death 1 (PD-1), and the other targets programmed cell death ligand 1 (PD-L1). These two belong to the class of immune checkpoint inhibitors (ICIs). However, immune-related adverse reactions (irAEs) were the main reasons affecting its clinical therapeutic effect. Methods: This retrospective cohort study analyzed red blood cell count (RBC), hematocrit (HCT), erythrocyte mean corpuscular volume (MCV) and immunotherapy outcomes in 920 lung cancer patients receiving immunotherapy from April 2019 to May 2023. Results: We found that high levels of RBC (>4.105 × 10⁹, p = 0.007, OR = 0.467, 95%CI: 0.268~0.812) and MCV (>86.35, p = 0.017, OR = 0.0.441, 95%CI: 0.224~0.865) were significantly related to the better response of ICIs immunotherapy in patients. Patients with high levels of HCT (>39.75%, p = 0.035, OR = 0.737, 95%CI: 0.555~0.979) may have a lower rate of irAEs occurrence. Meanwhile, patients with a low level of RBCs (≤4.635 × 10⁹, p < 0.001, OR = 1.636, 95%CI: 1.365~1.960) may have a longer period of PFS (progression-free survival), and patients with RBC (≤4.43 × 10⁹, p = 0.033, OR = 0.480, 95%CI: 0.244~0.941) may have a longer time of OS (overall survival). Conclusions: The findings indicate that the levels of RBC, MCV and HCT were significantly associated with the response and irAEs of ICIs in lung cancer patients. The levels of RBC might act as a possible biomarker for predicting the survival of lung cancer patients who are receiving ICI therapy. Full article

Simultaneous Localization and Mapping (SLAM) is crucial for the safe navigation of autonomous systems. Its accuracy is not based solely on the robustness of the algorithm employed or the metrological performances of the sensor, but rather on a combination of both factors. In this work, we present a comprehensive comparison framework for evaluating LiDAR-SLAM systems, focusing on key performance indicators including absolute trajectory error, uncertainty, number of tracked features, and computational time. Our case study compares two LiDAR-inertial SLAM configurations: one based on a motorized optomechanical scanner (the Ouster OS1) with a 360° field of view and the other based on MEMS scanners (the Livox Horizon) with a limited field of view and a non-repetitive scanning pattern. The sensors were mounted on a UGV for the experiments, where data were collected by driving the UGV along a predefined path at different speeds and angles. Despite substantial differences in field of view, detection range, and noise, both systems demonstrated comparable trajectory estimation performance, with average absolute trajectory errors of 0.25 m for the Livox-based system and 0.24 m for the Ouster-based system. These findings underscore the importance of sensor–algorithm co-design and demonstrate that even cost-effective, lower-field-of-view solutions can deliver competitive SLAM performance in real-world conditions. Full article

Earth hosts a remarkable diversity of life, with oceans covering over 70% of its surface and supporting the greatest abundance and variety of species, including a vast range of seaweeds. Among these, red seaweeds (Rhodophyta) represent the most diverse group and are particularly rich in bioactive compounds. Grateloupia turuturu Yamada and Porphyra umbilicalis Kütz. are two species with significant biotechnological and functional food potential. They contain high levels of phycobiliproteins, sulfated polysaccharides (e.g., carrageenan, agar, porphyran), mycosporine-like amino acids (MAAs), phenols, minerals, and vitamins, including vitamin B12 (rare among non-animal sources). Several analytical methods, such as spectrophotometry, chromatography, and mass spectrometry, have been used to characterize their chemical composition. In vitro and in vivo studies have demonstrated their antioxidant, anti-inflammatory, neuroprotective, immunostimulatory, anti-proliferative, and photoprotective effects. These bioactive properties support its application in the food, pharmaceutical, and cosmetic sectors. Given the growing demand for sustainable resources, these algae species stand out as promising candidates for aquaculture and the development of functional ingredients. Their incorporation into novel food products, such as snacks and fortified dairy and meat products, underscores their potential to support health-promoting diets. This review highlights G. turuturu and P. umbilicalis chemical richness, bioactivities, and applications, reinforcing their value as sustainable marine resources. Full article

This review article provides a comprehensive evaluation of Infuse^® and InductOs^®, two ground-breaking recombinant human Bone Morphogenetic Protein-2 (rhBMP-2)-based bone graft products, focusing on their tissue-level regenerative responses, clinical applications, and associated costs. Preclinical and clinical studies demonstrate that rhBMP-2 induces strong osteoinductive activity, effectively promoting mesenchymal stem cell differentiation and vascularized bone remodeling. While generally well-tolerated, these osteoinductive effects are dose-dependent, and excessive dosing or off-label use may result in adverse outcomes, such as ectopic bone formation or soft tissue inflammation. Histological and imaging analyses in craniofacial, orthopedic, and spinal fusion models confirm significant bone regeneration, positioning rhBMP-2 as a viable alternative to autologous grafts. Notably, advances in delivery systems and scaffold design have enhanced the stability, bioavailability, and targeted release of rhBMP-2, leading to improved fusion rates and reduced healing times in selected patient populations. These innovations, alongside its proven regenerative efficacy, underscore its potential to expand treatment options in cases where autografts are limited or unsuitable. However, the high initial cost, primarily driven by rhBMP-2, remains a critical limitation. Although some studies suggest overall treatment costs might be comparable to autografts when factoring in reduced complications and operative time, autografts often remain more cost-effective. Infuse^® has not substantially reduced the cost of bone regeneration and presents additional safety concerns due to the rapid (burst) release of growth factors and limited mechanical scaffold support. Despite representing a significant advancement in synthetic bone grafting, further innovation is essential to overcome limitations related to cost, mechanical properties, and controlled growth factor delivery. Full article

Background: Liver resection remains the gold standard treatment for colorectal cancer (CRC) liver metastases, while stereotactic body radiotherapy (SBRT) offers an alternative for patients with unresectable metastases. However, the precise indications for SBRT, optimal radiation doses, and treatment regimens have yet to be definitively established. Methods: A total of 91 patients with 152 lesions underwent SBRT, receiving a total dose ranging from 40 to 60 Gy delivered in 4–5 fractions per lesion, with a median dose of 50 Gy. Results: The three-year local control (LC) and overall survival (OS) rates were 62.6% and 45.1%, respectively. No cases of Grade ≥ 3 toxicity were observed. Factors negatively affecting LC included metastasis diameter ≥ 2.7 cm and number of metastases ≥ 3, with hazard ratios (HR) of 2.73 and 2.24, respectively. A biologically effective dose (BED) of ≥ 137.7 Gy was associated with a significant improvement in local control (LC) (HR 0.25), a finding that was also confirmed by the inverse probability of treatment weighting (IPTW) analysis. Significant predictors for poorer OS included RAS gene mutations, metastasis diameter ≥ 2.6 cm, and synchronous metastases, with HRs of 2.27, 2.03, and 2.11, respectively. Landmark analysis demonstrated that local recurrence within 12 months after SBRT significantly reduced OS (HR 2.68). Conclusions: SBRT is a safe and effective method for achieving local control of CRC liver oligometastases. Further research is warranted to optimize treatment protocols and refine patient selection criteria. Full article

Singlet oxygen (¹O₂), a reactive oxygen species, can oxidize lipids, proteins, and DNA at high concentrations, leading to cell death. Despite its extremely short half-life (10⁻⁵s), ¹O₂ acts as a critical signaling molecule, triggering a retrograde pathway from chloroplasts to the nucleus to regulate nuclear gene expression. In this study, rice seeds were treated with 0, 5, 20 and 80 μM Rose Bengal (RB, a photosensitizer) under moderate light for 3 days to induce ¹O₂ generation. Treatment with 20 μM RB reduced stomatal density by approximately 25% in three-leaf-stage rice seedlings, while increasing the contents of pectin, hemicellulose, and cellulose in root cell walls by 30–40%. Under drought, salinity, or shading stress, 20 μM RB treatment significantly improved rice tolerance, as evidenced by higher relative water contents (49–58%) and chlorophyll contents (60–76%) and lower malondialdehyde (37–43%) and electrolyte leakage (29–37%) compared to the control. Moreover, RT-qPCR analysis revealed that the significant up-regulation of stomatal development genes (OsTMM and OsβCA1) and cell wall biosynthesis genes (OsF8H and OsLRX2) was associated with RB-induced ¹O₂ production. Thus, under controlled environmental conditions, ¹O₂ may regulate stomatal development and cell wall remodeling to enhance rice tolerance to multiple abiotic stresses. These results provide new perspectives for the improvement of rice stress tolerance. Full article

Purpose: Evaluation of predictors and outcomes in NSCLC patients treated with an immune checkpoint inhibitor (ICI) following a severe immune-related adverse event (irAE). Methods: We included all NSCLC patients receiving ≥1 ICI cycle and corticosteroids for CTCAE Grade ≥3 irAEs between 2017 and 2023 from three UK NHS teaching hospitals. Progression-free survival (PFS) and overall survival (OS) after the 1st irAE, best overall response (BOR) to ICI, and predictors of clinical benefit were evaluated. Kaplan–Meier, Cox and logistic regression models, and Wilcoxon tests were used. Results: We screened 1658 NSCLC patients and identified 80 eligible subjects. The majority of patients had metastatic (n = 50, 63%) vs. localized (n = 30, 37%) NSCLC. Most patients developed a single ≥Grade 3 irAE on 1st line ICI (n = 71, 89%). Overall, 14 (18%) patients developed 2nd irAEs, 7 after rechallenge with ICIs. In the complete cohort, median OS after 1st irAE was 15.84 months (95% CI, 12.45–26.91). Lower neutrophil-to-lymphocyte ratio (NLR), patients receiving >4 cycles of ICI or median duration of ICI of >2.76 months before 1st irAE were associated with improved OS (p < 0.05), the latter two with PFS (p < 0.05). Age, gender, stage, KRAS mutation, PD-L1 and ICI type were not associated with PFS or OS. Pneumonitis as 1st irAE had the worst PFS and OS (p < 0.05). Median starting corticosteroid dose of ≤60 mg for 1st irAE had an improved OS (p = 0.04). Post 1st irAE response associated with better PFS and OS (p < 0.05). Number and duration of irAEs and additional immunosuppressive agents (14% of patients) were not associated with PFS or OS. Conclusions: In ≥Grade 3 irAEs patients managed with corticosteroids, lower baseline NLR, longer ICI use, response to ICI after 1st irAE, and a ≤60 mg corticosteroid dose had promising outcomes. Full article

Background: Metastatic pancreatic cancer (mPC) is an aggressive disease with high morbidity and mortality, and long-term survival rates remain poor. New therapeutic options that demonstrate statistically significant improvements in overall survival (OS) and progression-free survival (PFS) are still being sought. Although many first-line (FL) treatment studies exist in the literature, there are almost no prospective studies on second-line (SL) therapy. Methods: The aim of this clinical study was to retrospectively analyze the medical history of 251 patients diagnosed with mPC, treated first-line (FL) with GEM-NAB between February 2017 and January 2025. After disease progression, 109 patients received SL treatment. We also present a multivariate analysis based on routinely collected data (demographic, clinical, and laboratory parameters) evaluating their impact on OS and PFS. Results: The median age was 66 years (range 37–84 years). The median PFS was 2.33 months (95% CI 1.69–2.97). Specifically, the mPFS was 4.1 months (95% CI 1.31–6.90) for FOLFIRINOX; 2.8 months (95% CI 2.30–3.30) for FOLFIRI; 2.37 months (95% CI 1.66–3.08) for NALIRI; 1.47 months (95% CI 1.18–1.75) for FOLFOX 6; and 0.93 months (95% CI 0.00–2.64) for GEM-cisplatin. The median OS was 5.03 months (95% CI 3.75–6.31). Seven patients achieved a partial response (overall response rate 6%). The most frequent adverse events (AEs) included anemia, fatigue, peripheral neuropathy, neutropenia, and thrombocytopenia. Conclusions: As a result, SL treatments were compared, and some statistically significant difference was found between them in PFS time for chemotherapy FOLFIRINOX and GEM + cisplatin. The most frequent AEs occurred during treatment with FOLFIRINOX chemotherapy. Full article

Background: Breast cancer is frequently diagnosed in older women. However, the impact of surgery on survival is not well studied and prognosis for women ≥ 80 years of age is progressively depending on comorbidities. Methods: Medical records of consecutive women aged ≥ 80 years diagnosed with primary breast cancer treated with upfront surgery at two Breast Centers from 2011 to 2021 were retrospectively analyzed. Results: A total of 553 consecutive women with a median age of 83 years and a median tumor diameter of 21 mm were analyzed (574 lesions). Clinical Stages II or III were found in 263/574 (46%) and 101/574 cases (18%), respectively. Axillary staging was completely omitted for 94/542 invasive lesions (17%), and this increased over time from 2% to 33% (p < 0.001). Adjuvant hormone therapy and radiotherapy were omitted in 134/490 (27%) and in 122/420 patients (29%), respectively, while only 26/195 (13%) of patients with a clear clinical indication received adjuvant chemotherapy. At a median follow-up of 61 months (6–147) the 5- and 10-years overall survival (OS) were 64% and 21%, while breast cancer-specific survival (BCSS) at 5 and 10 years were 94% and 78%, respectively. Adjuvant therapies were not associated with a significant improvement in BCSS, while worse OS was associated with older age or more comorbidities as measured by the Charlson Comorbidity Index (CCI) (p < 0.001 and p = 0.012, respectively). Conclusions: Breast surgery, when possible, has a primary role even for women > 80 years of age, and it is associated with a reasonable BCSS. De-escalation of adjuvant therapies should be considered in this setting because survival is largely determined by age and co-morbidities. Full article

Objective: This study aimed to investigate the prognostic value of the preoperative monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and clinicopathological parameters for predicting survival outcomes in patients undergoing curative-intent gastrectomy for gastric adenocarcinoma. Methods: This retrospective cohort study analyzed data from 304 patients with histopathologically confirmed gastric adenocarcinoma who underwent curative-intent gastrectomy with standardized D1+ or D2 lymphadenectomy. The MHR was calculated using preoperative monocyte counts and HDL cholesterol levels. Patients were dichotomized based on the optimal MHR cutoff determined via receiver operating characteristic curve analysis with the Youden index. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were assessed using Kaplan–Meier analysis and compared with log-rank tests. Results: ROC analysis determined an optimal MHR cutoff of ≥11.02 (AUC: 0.654; 95% CI: 0.59–0.718), yielding sensitivities and specificities of 62.6% and 62.4%, respectively. Patients with an elevated MHR (≥11.02) had worse 5-year OS (51.4 vs. 72.2%; p < 0.001) and PFS (65.2 vs. 80.5%; p = 0.003). In the multivariate Cox regression model, elevated MHR emerged as an independent predictor of disease progression (HR: 1.93; 95% CI: 1.17–3.18; p = 0.010), while parameters such as signet ring cell histology, lymphovascular invasion, and perineural invasion were significant in univariate analyses but not in the adjusted multivariate model. Conclusions: MHR should not be regarded as a definitive predictor in isolation but rather as a cost-effective, readily obtainable adjunct within a broader preoperative risk assessment framework. Integration with other inflammation-based and clinicopathological factors may enhance predictive performance and clinical applicability. Full article

Background/Objectives: Biliary tract cancers (BTCs), encompassing tumors of the bile ducts, gallbladder, or ampulla of Vater, are notoriously hard to manage, especially when surgery is off the table and standard chemotherapy provides only modest benefits. While emerging treatments such as immune checkpoint inhibitors have shown promise, mixed clinical trial results and varied study endpoints have left their true impact unclear. This concise review consolidates current evidence on combining chemotherapy with immunotherapy to clarify whether these regimens can significantly improve outcomes and steer more effective treatment strategies for BTCs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) and prospective comparative studies published from January 2010 to December 2024. Fixed-effect meta-analyses (inverse-variance method) were used as the primary approach, with random-effects models (REML) performed as sensitivity analyses to confirm robustness were performed to calculate pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). Leave-one-out sensitivity analyses and Egger’s tests assessed result stability and publication bias. The review was conducted in accordance with PRISMA 2020 guidelines and registered in OSF. Results: Two RCTs (n = 1754; chemoimmunotherapy n = 874, chemotherapy n = 880) were included in the quantitative meta-analysis. Compared to chemotherapy alone, chemoimmunotherapy significantly reduced the risk of death by 20% (OS, HR = 0.80; 95% CI 0.72–0.89; I² = 0%) and the risk of disease progression or death by 19% (PFS, HR = 0.81; 95% CI 0.73–0.90; I² = 33.5%). Leave-one-out sensitivity analyses confirmed result stability. Egger’s tests showed no significant publication bias (OS p = 0.30; PFS p = 0.40). Two additional studies (IMbrave 151 and Monge 2022) lacking comparative survival data were qualitatively assessed. Conclusions: Chemoimmunotherapy significantly improves OS and PFS compared with chemotherapy alone in advanced BTC, with consistent findings across included trials. These results support the incorporation of chemoimmunotherapy as a first-line therapeutic strategy. Future research should prioritize biomarker-driven patient selection, evaluation of long-term clinical outcomes, and integration of targeted therapies with chemoimmunotherapy. Full article